Maternal folic acid supplementation with Vitamin B 12 deficiency during pregnancy and lactation affects the metabolic health of adult female offspring but is dependent on offspring diet

Abstract

Epidemiologic studies have reported relationships between maternal high folate and/or low B 12 status during pregnancy and greater adiposity and insulin resistance in children. The goal of this study was to determine the effects of maternal folic acid supplementation (10 mg/kg diet), with (50 mg/kg diet) and without B 12 , on adult female offspring adiposity and glucose homeostasis. Female C57BL/6J mice were fed 1 of 3 diets from weaning and throughout breeding, pregnancy, and lactation: control (2 mg/kg diet folic acid, 50 mg/kg diet B 12 ), supplemental folic acid with no B 12 (SFA2B 12 ), or supplemental folic acid with adequate B 12 (SFA+B 12 ). Female offspring were weaned onto the control diet or a Western diet (45% energy fat, 2 mg/kg diet folic acid, 50 mg/kg diet B 12 ) for 35 wk. After weaning, control diet-fed offspring with SFA2B 12 dams had fasting hyperglycemia, glucose intolerance, lower b cell mass, and greater islet hepatocyte nuclear factor 1 homeobox a and nuclear receptor subfamily 1 group H member 3 mRNA than did offspring from control dams. In Western diet-fed offspring, those with SFA2B 12 dams had lower fasting blood glucose and plasma insulin concentrations, and were smaller than control offspring. Our findings suggest that maternal folic acid supplementation with B 12 deficiency during pregnancy/lactation programs the metabolic health of adult female offspring but is dependent on offspring diet.